Erythropoiesis ; physiology ; Humans ; Mitochondria ; physiology ; Mitochondrial Degradation

Autophagy is a physiological process which delivers the mutant cytoplasmic proteins and dysfunctional subcellular organs into lysosomes for degradation to generate fuel in the deficiency conditions. It is mainly classified into macroautophagy, microautophagy and chaperon-mediated autophagy (CMA), as well as the selective autophagy such as mitophagy and aggrephagy. This review mainly introduces the key molecular markers of macroautophagy, CMA and mitophagy.
Autophagy ; Humans ; Lysosomes ; Mitochondrial Degradation ; Molecular Chaperones

Mitochondria are small organelles that produce the majority of cellular energy as ATP. Mitochondrial dysfunction has been implicated in the pathogenesis of Parkinson's disease (PD), and rare familial forms of PD provide valuable insight into the pathogenic mechanism underlying mitochondrial impairment, even though the majority of PD cases are sporadic. The regulation of mitochondria is crucial for the maintenance of energy-demanding neuronal functions in the brain. Mitochondrial biogenesis and mitophagic degradation are the major regulatory pathways that preserve optimal mitochondrial content, structure and function. In this mini-review, we provide an overview of the mitochondrial quality control mechanisms, emphasizing regulatory molecules in mitophagy and biogenesis that specifically interact with the protein products of three major recessive familial PD genes, PINK1, Parkin and DJ-1.
Adenosine Triphosphate ; Brain ; Homeostasis* ; Mitochondria ; Mitochondrial Degradation ; Neurons ; Organelles ; Parkinson Disease* ; Quality Control ; Organelle Biogenesis

Mitophagy is a process during which the cell selectively removes the mitochondria via the mechanism of autophagy. It is crucial to the functional completeness of the whole mitochondrial network and determines cell survival and death. On the one hand, the damaged mitochondria releases pro-apoptotic factors which induce cell apoptosis; on the other hand, the damaged mitochondria eliminates itself via autophagy, which helps to maintain cell viability. Mitophagy is of vital importance for the development and function of the nervous system. Neural cells rely on autophagy to control protein quality and eliminate the damaged mitochondria, and under normal circumstances, mitophagy can protect the neural cells. Mutations in genes related to mitophagy may cause the development and progression of neurodegenerative diseases. An understanding of the role of mitophagy in nervous system diseases may provide new theoretical bases for clinical treatment. This article reviews the research advances in the relationship between mitophagy and different types of nervous system diseases.
Apoptosis ; Autophagy ; physiology ; Humans ; Mitochondrial Degradation ; Nervous System Diseases ; etiology ; Neurodegenerative Diseases ; etiology

Mitochondria play a key role in various cell processes including ATP production, Ca homeostasis, reactive oxygen species (ROS) generation, and apoptosis. The selective removal of impaired mitochondria by autophagosome is known as mitophagy. Cerebral ischemia is a common form of stroke caused by insufficient blood supply to the brain. Emerging evidence suggests that mitophagy plays important roles in the pathophysiological process of cerebral ischemia. This review focuses on the relationship between ischemic brain injury and mitophagy. Based on the latest research, it describes how the signaling pathways of mitophagy appear to be involved in cerebral ischemia.
Animals ; Brain Ischemia ; metabolism ; pathology ; Humans ; Mitochondrial Degradation ; Reactive Oxygen Species ; metabolism ; Stroke ; metabolism ; pathology

Parkinson's disease (PD) is the second most common neurodegenerative motor disorder, affecting approximately 1% of the population aged > or =60 years. Recent investigations have shown that in addition to motor symptoms such as bradykinesia, resting tremor, and gait instability, PD also causes non-motor symptoms such as insomnia, constipation, depression, and dementia. Most PD cases occurred sporadically, but 5-10% is inherited as familial PD, and several PD-causative genes have been identified and intensively studied. Autophagy is a self-degrading mechanism of balancing the energy source in response to nutrient shortage and various stresses, and is a tightly regulated and complicated process that generates double-membrane organelles. Autophagy failure has recently been observed in both animal PD models and human PD patients. The intention of this review is to introduce recent findings regarding the relationship between causative genetic mutations in PD and autophagy, from a clinical perspective.
Animals ; Autophagy* ; Constipation ; Dementia ; Depression ; Gait ; Humans ; Hypokinesia ; Intention ; Mitochondrial Degradation ; Organelles ; Parkinson Disease* ; Sleep Initiation and Maintenance Disorders ; Tremor

OBJECTIVETo investigate mitophagy in an animal model of hypoxic-ischemic brain damage (HIBD) and its role in HIBD.

METHODSA total of 120 neonatal Sprague-Dawley rats aged 7 days were divided into three groups: sham-operation, HIBD, and autophagy inhibitor intervention (3MA group). The rats in the HIBD group were treated with right common carotid artery ligation and then put in a hypoxic chamber (8% oxygen and 92% nitrogen) for 2.5 hours. Those in the 3MA group were given ligation and hypoxic treatment at 30 minutes after intraperitoneal injection of 2 μL 3MA. Those in the sham-operation group were not given ligation or hypoxic treatment. Single cell suspension was obtained from all groups after model establishment. Immunofluorescence localization was performed for mitochondria labeled with MitoTracker, autophagosomes labeled with LysoTracker, and autophagy labeled with LC3 to observe mitophagy. After staining with the fluorescent probe JC-1, flow cytometry was used to measure mitochondrial membrane potential. TTC staining was used to measure infarct volume. Cytoplasmic proteins in cortical neurons were extracted, and Western blot was used to measure the expression of mitophagy-related proteins.

RESULTSCompared with the sham-operation group, the HIBD group had a significant reduction in mitochondrial membrane potential (P<0.05), a significant increase in mitophagy (P<0.05), a significant increase in the expression of the proteins associated with the division of the mitochondrial Drp1 and Fis1 (P<0.05), and a significant reduction in the expression of the mitochondrial outer membrane protein Tom20 and the mitochondrial inner membrane protein Tim23 (P<0.05). Compared with the HIBD group, the 3MA group had a significantly greater reduction in mitochondrial membrane potential (P<0.05), but showed significantly reduced mitophagy (P<0.05). In addition, the 3MA group had a significantly increased degree of cerebral infarction compared with the HIBD group (P<0.05).

CONCLUSIONSHIBD can increase the degree of mitophagy, and the inhibition of mitophagy can aggravate HIBD in neonatal rats.

Animals ; Animals, Newborn ; Female ; Hypoxia-Ischemia, Brain ; etiology ; physiopathology ; Male ; Mitochondrial Degradation ; physiology ; Rats ; Rats, Sprague-Dawley

Despite considerable efforts to prevent and treat cardiovascular disease (CVD), it has become the leading cause of death worldwide. Cardiac mitochondria are crucial cell organelles responsible for creating energy-rich ATP and mitochondrial dysfunction is the root cause for developing heart failure. Therefore, maintenance of mitochondrial quality control (MQC) is an essential process for cardiovascular homeostasis and cardiac health. In this review, we describe the major mechanisms of MQC system, such as mitochondrial unfolded protein response and mitophagy. Moreover, we describe the results of MQC failure in cardiac mitochondria. Furthermore, we discuss the prospects of 2 drug candidates, urolithin A and spermidine, for restoring mitochondrial homeostasis to treat CVD.
Adenosine Triphosphate ; Cardiovascular Diseases ; Cause of Death ; Heart Failure ; Heart ; Homeostasis ; Mitochondria ; Mitochondrial Degradation ; Organelles ; Quality Control ; Spermidine ; Unfolded Protein Response

Mitochondria participate in various intracellular metabolic pathways such as generating intracellular ATP, synthesizing several essential molecules, regulating calcium homeostasis, and producing the cell's reactive oxygen species (ROS). Emerging studies have demonstrated newly discovered roles of mitochondria, which participate in the regulation of innate immune responses by modulating NLRP3 inflammasomes. Here, we review the recently proposed pathways to be involved in mitochondria-mediated regulation of inflammasome activation and inflammation: 1) mitochondrial ROS, 2) calcium mobilization, 3) nicotinamide adenine dinucleotide (NAD+) reduction, 4) cardiolipin, 5) mitofusin, 6) mitochondrial DNA, 7) mitochondrial antiviral signaling protein. Furthermore, we highlight the significance of mitophagy as a negative regulator of mitochondrial damage and NLRP3 inflammasome activation, as potentially helpful therapeutic approaches which could potentially address uncontrolled inflammation.
Adenosine Triphosphate ; Calcium ; Cardiolipins ; DNA, Mitochondrial ; Homeostasis ; Immunity, Innate ; Inflammasomes* ; Inflammation ; Metabolic Networks and Pathways ; Mitochondria* ; Mitochondrial Degradation ; NAD ; Reactive Oxygen Species

This study surveys the improvement characteristics in old-aged muscular mitochondria by bio-active materials coated fabric (BMCF). To observe the effects, the fabric (10 and 30%) was worn to old-aged rat then the oxygen consumption efficiency and copy numbers of mitochondria, and mRNA expression of apoptosis- and mitophagy-related genes were verified. By wearing the BMCF, the oxidative respiration significantly increased when using the 30% materials coated fabric. The mitochondrial DNA copy number significantly decreased and subsequently recovered in a dose-dependent manner. The respiratory control ratio to mitochondrial DNA copy number showed a dose-dependent increment. As times passed, Bax, caspase 9, PGC-1alpha and beta-actin increased, and Bcl-2 decreased in a dose-dependent manner. However, the BMCF can be seen to have had no effect on Fas receptor. PINK1 expression did not change considerably and was inclined to decrease in control group, but the expression was down-regulated then subsequently increased with the use of the BMCF in a dose-dependent manner. Caspase 3 increased and subsequently decreased in a dose-dependent manner. These results suggest that the BMCF invigorates mitophagy and improves mitochondrial oxidative respiration in skeletal muscle, and in early stage of apoptosis induced by the BMCF is not related to extrinsic death-receptor mediated but mitochondria-mediated signaling pathway.
Actins ; Animals ; Antigens, CD95 ; Apoptosis ; Caspase 3 ; Caspase 9 ; DNA, Mitochondrial ; Mitochondria* ; Mitochondrial Degradation ; Muscle, Skeletal ; Oxygen Consumption ; Rats* ; Respiration ; RNA, Messenger